We propose to continue our studies characterizing the influence of substrates of extracellular matrix on the maintenance of differentiated epithelial cells in culture. A form of extracellular matrix, called biomatrix, is isolated by methods developed previously. Studies with biomatrix indicate that it is tissue- and species-specific both for chemical composition and for ability to sustain cells in culture. Differentiated epithelial cells such as prostatic epithelial cells or insulinoma cells can be maintained in vitro long-term if cultured on substrates of biomatrix. They continue to express some of their known tissue-specific functions. We want to complete the characterization of cultures of insulinomas and prostatic carcinomas maintained on various substrates, most importantly, tissue-and species-specific biomatrix. Information derived from these studies will be used to establish cultures of normal human prostatic epithelium and normal human islet cells. Our studies will include experiments to clarify the empirical findings of tissue- and species-specificity of biomatrix. Chemical characterization of human pancreatic and prostatic biomatrix will form the basis for studies in which the components of the biomatrix critical for maintenance of the differentiated functions are to be found. New forms of substrates will then be made containing only these critical components.